Project Summary The long-term goal of our research is to understand how the sensory environment regulates animal behavior. In the next five years, we propose to investigate the neural and genetic basis of two types of sensory modalities: thermosensation and chemosensation. Thermosensation and chemosensation are critical for the quality and survival of all forms of life ranging from bacteria to humans. To survive and thrive, animals and humans have evolved thermosensory and chemosensory systems to detect, respond, and adapt to temperature and chemicals in the environment. Defects in thermal and chemical perception lead to neurological and metabolic disorders. Nevertheless, our understanding of the mechanisms underlying thermosensation and chemosensation is far from complete. For example, though research in the past two decades has led to an increasingly clear understanding of how animals sense heat, which reveals a remarkable conservation in the mechanisms of thermosensation, much less is known about how animals sense cold temperatures. Similarly, in the case of pH sensation, a type of chemosensation, though acid sensation has been extensively characterized, we know very little about how animals sense alkali in the environment. Here, we will investigate the neural and genetic mechanisms underlying cold sensation and alkaline sensation in C. elegans, a powerful genetic organism widely used for the study sensory perception. To do so, we will use a multidisciplinary approach combining behavioral, genetic, calcium imaging, and electrophysiological analyses. As thermosensory and chemosensory mechanisms particularly those involving sensory channels/receptors tend to be evolutionarily conserved, our work will provide novel insights into the mechanisms underlying these sensory modalities in mammals and related neurological and metabolic disorders.